Disagreement in high-grade/low-grade intraepithelial neoplasia and high-risk/low-risk HPV infection: clinical implications for anal cancer precursor lesions in HIV-positive and HIV-negative MSM

Background We report the prevalence and predictors for high-grade anal intraepithelial neoplasia (HGAIN) in community-based cohorts of HIV-negative and HIV-positive homosexual men in Sydney, Australia. Methods: A cross-sectional study of consecutive participants in both cohorts was performed in 2005 (204 HIV-negative and 128 HIV-positive men). Anal swabs collected by a research nurse underwent cytological analysis, using the ThinPrep procedure, and human papillomavirus (HPV) testing. Participants who had cytological abnormalities other than low-grade squamous epithelial lesions (SIL) were referred for high resolution anoscopy (HRA). Results: A total of 114 men had cytological abnormalities (24.3% of HIV-negative and 57.5% of HIV-positive men, odds ratio (OR) = 4.21, 95% confidence interval (CI) 2.57–6.90). However, only three (2.3%) HIV-positive men and no HIV-negative men had high-grade SIL on anal cytology. Seventy-seven men were referred for HRA, of whom 63 (81.8%) attended. Histologically confirmed HGAIN was detected in 21 (33.3%). The prevalence of HGAIN was higher in HIV-positive men (10.8%) than in HIV-negative men (5.0%, OR = 2.29, 95% CI 0.93–5.63, P = 0.071). HGAIN was not related to age but was strongly associated with the detection of high-risk types of anal HPV (OR = 10.1, 95% CI 1.33–76.2) rather than low-risk types (OR = 1.97, 95% CI 0.74–5.25). Conclusion: HGAIN was prevalent in homosexual men across all age groups and was more than twice as common in HIV-positive men compared with HIV-negative men. The presence of high-risk anal HPV was highly predictive of HGAIN.

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The reporting of anal cytology and histology samples: establishing terminology and criteria

Sexual Health ◽

10.1071/sh10140 ◽

2012 ◽

Vol 9 (6) ◽

pp. 562 ◽

Cited By ~ 6

Author(s):

Jennifer Margaret Roberts ◽

Deborah Ekman

Keyword(s):

Reporting System ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Classification Systems ◽

Low Grade ◽

Evidence Based ◽

High Grade ◽

Anal Neoplasia ◽

Anal Cytology ◽

Bethesda System

Our understanding of the human papillomavirus (HPV) related cytomorphology and histopathology of the anal canal is underpinned by our knowledge of HPV infection in the cervix. In this review, we utilise cervical reporting of cytological and histological specimens as a foundation for the development of standardised and evidence-based terminology and criteria for reporting of anal specimens. We advocate use of the Australian Modified Bethesda System 2004 for reporting anal cytology. We propose the use of a two-tiered histological reporting system for noninvasive disease – low-grade and high-grade anal intraepithelial neoplasia. These classification systems reflect current understanding of the biology of HPV and enhance diagnostic reproducibility. Biomarkers such as p16INK4A may prove useful in further improving diagnostic accuracy. Standardisation is important because it will increase the value of the data collected as Australian centres develop programs for screening for anal neoplasia.

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Vroegtijdige opsporing van voorstadia van een anaal carcinoom bij hiv-seropositieve patiënten

Tijdschrift voor Geneeskunde ◽

10.47671/tvg.77.21.129 ◽

2021 ◽

Author(s):

E. GÖKCE ◽

J. GELDOF ◽

P. ROELANDT ◽

J. VAN DORPE ◽

S. CALLENS ◽

...

Keyword(s):

Anal Cancer ◽

Digital Rectal Examination ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

High Grade ◽

Anal Squamous Cell Carcinoma ◽

Increased Risk ◽

High Prevalence ◽

Risk Patients ◽

Hiv Seropositive

Early detection of precursor lesions of anal cancer in HIV-seropositive patients Although anal cancer is rare in the overall population, its incidence is increasing in the last decades. Especially HIV-seropositive patients have an increased risk of developing anal squamous cell carcinoma (SCC), mainly because of the high prevalence of high-grade anal intraepithelial neoplasia (AIN) among these patients. High-grade AIN is a precursor lesion for anal SCC associated with human papillomavirus (HPV) infection. Despite the lack of direct evidence demonstrating that AIN identification reduces the risk of anal cancer, experts think that screening and treatment of high-risk patients will prevent the disease. This article aims to review the current literature about AIN and discusses the screening options, including digital rectal examination, anal cytology and high-resolution anoscopy.

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Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502011000600019 ◽

2011 ◽

Vol 26 (6) ◽

pp. 521-529 ◽

Cited By ~ 3

Author(s):

Adriana Gonçalves Daumas Pinheiro Guimarães ◽

Roberto Moreira da Silva Junior ◽

Oscar Tadeu Ferreira da Costa ◽

Ivan Tramujas da Costa e Silva ◽

Felicidad Santos Gimenez ◽

...

Keyword(s):

Dendritic Cells ◽

Viral Load ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Relative Volume ◽

Significant Rise ◽

Anal Intraepithelial Neoplasia ◽

Hiv Positive ◽

Hiv 1 ◽

Hiv Negative

PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV induces the recovery of the density of epithelial DC.

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The Role of Early Colposcopy in the Management of Females with First Episode Anogenital Warts

International Journal of STD & AIDS ◽

10.1177/095646249400500511 ◽

1994 ◽

Vol 5 (5) ◽

pp. 343-345 ◽

Cited By ~ 2

Author(s):

K A Ward ◽

J R Houston ◽

B E Lowry ◽

R D Maw ◽

W W Dinsmore

Keyword(s):

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Cervical Cytology ◽

First Episode ◽

Low Grade ◽

High Grade ◽

Anogenital Warts ◽

Cervical Smear ◽

Cervical Lesions ◽

Increased Risk

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear ( P<0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.

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29. WHAT DO ANAL CYTOLOGY RESULTS MEAN?

Sexual Health ◽

10.1071/shv4n4ab29 ◽

2007 ◽

Vol 4 (4) ◽

pp. 296

Author(s):

R. Hillman

Keyword(s):

Anal Cancer ◽

Screening Program ◽

Cervical Screening ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

High Grade ◽

Retrospective Case ◽

Screening Programs ◽

Anal Dysplasia ◽

Anal Swab

Background: Between 1970 and 2000 in Australia, anal cancer rates have increased over fourfold. Furthermore, the prevalence rate of anal cancer in MSM is approximately 35 cases/100�000, comparable to that of cervical cancer in women prior to the introduction of the national cervical screening program. These observations have led to calls for the introduction of targeted anal cytological screening program for MSMs. Our study examined the effectiveness of anal cytological testing in detecting histologically proven high grade anal intraepithelial neoplasia (HGAIN, also known as AIN2 & 3). Methods: A retrospective case note review of people attending an anal dysplasia clinic from July 2002 to May 2007 was performed. Cytological results of anal swabs were compared to results of biopsies obtained through high resolution anoscopy. Results: 436 anal cytological results were identified. Of these, 5% were unsatisfactory, 51% showed low grade changes and 44% showed high grade changes. 185 cases were then paired with corresponding histological results. Analysing the data from the perspective of diagnosing histologically proven HGAIN, anal swab cytological abnormalities revealed a sensitivity of 54% and specificity of 90% for the most recent cytological test and 83% and 39% respectively, when analysed according to most serious cytological result ever. Conclusions: Our sensitivities of 54-83% and specificities of 39-90% are consistent with those found with cervical cytology, but emphasize the need for caution in their interpretation. However, before any anal cytological screening programs are introduced, it is important to also establish that treatment of any high grade anal dysplasia detected by such screening is of value in preventing progression to cancer.

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Risk, Persistence and Multiplicity of HPV Infections among HIV Negative and HIV Positive Nigerian Women

Journal of Global Oncology ◽

10.1200/jgo.2016.003830 ◽

2016 ◽

Vol 2 (3_suppl) ◽

pp. 38s-39s

Author(s):

Sally N. Adebamowo ◽

Toyosi Olawande ◽

Ayotunde Famooto ◽

Eileen O. Dareng ◽

Olayinka Olaniyan ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Hpv Infection ◽

Hiv Positive ◽

P Value ◽

Increased Risk ◽

Hiv Women ◽

Dna Enzyme Immunoassay ◽

High Risk Hpv ◽

Hiv Negative

Abstract 64 Background: The incidence, prevalence, persistence, and multiplicity of high-risk HPV infection is different between HIV positive and HIV negative women. We examined the association between HIV, prevalent HPV, and persistent HPV infections among women in a prospective cohort in Nigeria. Methods: We enrolled women presenting at cervical cancer screening programs in Abuja, Nigeria, between 2012 and 2014 and collected information on their demographic characteristics, risk factors of HPV infection, and cervical exfoliated cells samples at baseline, 6 month and 12 month follow-up visits. DNA enzyme immunoassay (DEIA) and Roche Linear Array HPV Genotyping Test were used to characterize HPV. Persistent HPV infection was defined as a positive result on 2 consecutive DEIA tests. We used logistic regression models to estimate the association between HIV and risk of HPV infection. Results: Among the 1,020 women enrolled, the mean age (±SD) was 37(8), and 44% and 56% were HIV+ and HIV-, respectively. HPV52 and 35 were the most common HPV types in the study population. The prevalence was 34% for any HPV, 24% for persistent HPV and 9% for multiple HPV infections; these were higher among HIV+ women (p-value <0.001). The multivariate odds ratio (OR) and 95 % CI comparing HIV+ to HIV- women was 6.29 (95% CI 3.64 – 10.87, p-value <0.001) for any high-risk HPV; 6.22 (95% CI 3.02 – 12.83, p-value <0.001) for persistent high-risk HPV; and 6.46 (95% CI 2.69 – 15.52, p-value <0.001) for multiple high-risk HPV infections, Conclusions: HIV infection is associated with increased risk of persistence and multiplicity of low-risk and high-risk HPV infections. These findings may explain, in part, the increased risk of cervical cancer among women with HIV infections. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Sally N. Adebamowo No relationship to disclose Toyosi Olawande No relationship to disclose Ayotunde Famooto No relationship to disclose Eileen O. Dareng No relationship to disclose Olayinka Olaniyan No relationship to disclose Richard Offiong No relationship to disclose Clement A. Adebamowo Speakers' Bureau: Merck [Table: see text]

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The Prevalence of High Carcinogenic Risk of HPV Genotypes among HIV-Positive and HIV-Negative MSM from Russia

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2021/6641888 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Ilia Beliakov ◽

Maria Senina ◽

Yuriy Tyulenev ◽

Elena Novoselova ◽

Viktor Surovtsev ◽

...

Keyword(s):

High Risk ◽

Hiv Infection ◽

Hpv Infection ◽

Carcinogenic Risk ◽

Hiv Positive ◽

Hiv Status ◽

Hpv Genotypes ◽

Hpv Types ◽

Sex With Men ◽

Hiv Negative

Objective. Men who have sex with men (MSM) have a high risk of lifelong anal cancer caused by high-risk human papillomavirus (HR HPV) infections. The aim of this study was to investigate the prevalence of anal canal HR HPV infection among men who have sex with men (MSM) with and without HIV infection in Moscow (Russia). We evaluated associations of some HIV coinfections (HSV and CMV) and HPV distribution among MSM with and without HIV infection. Methods. Two groups of HIV-positive (n = 60) and HIV-negative (n = 60) MSM were evaluated in the study. Fourteen high-risk (HR) HPV types, HSV1/2, and CMV were investigated in men anal swabs. Results. HR HPVs were found with nearly the same frequency of 66.7% in both groups: HIV-positive and HIV-negative MSM. HIV-positive status was statistically associated with the presence of several (more than two) HPV types ( p = 0.044 ). The most prevalent HR HPV genotypes were HPV18, HPV16, HPV56, and HPV33 for HIV-positive MSM and HPV56, HPV51, HPV66, and HPV16 for HIV-negatives. We found a statistically significant association of five HR HPV types with HIV status of MSM: HPV16 ( p = 0.028 ), HPV18 ( p = 0.00006 ), HPV58 ( p = 0.003 ), HPV33 ( p = 0.019 ), and HPV39 ( p = 0.026 ). The frequency of HSV1 (1.7%) and HSV2 (10%) infections and CMV (3.3%) infection was evaluated in the group of HIV-positive MSM. The frequency of HSV1 (5%) and HSV2 (6.7%) infections and CMV (0%) infection was evaluated, as well, in the group of HIV-negative MSM. Conclusion. Multiple HPV genotypes were detected significantly more often than single HPV genotype in the group of HIV-positive MSM. According to our data, 25% of HIV-positive MSM have HPV39; this is the only one of the five types of HR HPV (16, 18, 58, 33, and 39) associated with this group of MSM that has not yet been included in the HPV vaccines available on the market.

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Clearance of Type-Specific, Low-Risk, and High-Risk Cervical Human Papillomavirus Infections in HIV-Negative and HIV-Positive Women

Journal of Global Oncology ◽

10.1200/jgo.17.00129 ◽

2018 ◽

pp. JGO.17.00129

Author(s):

Sally N. Adebamowo ◽

Ayotunde Famooto ◽

Eileen O. Dareng ◽

Oluwatoyosi Olawande ◽

Olayinka Olaniyan ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Hpv Infection ◽

Low Risk ◽

Hiv Positive ◽

Hiv Positive Women ◽

Study Population ◽

Study Participants ◽

Cervical Human Papillomavirus ◽

Hiv Negative

Purpose There is a dearth of data on clearance of cervical human papillomavirus (HPV) infection among women in West Africa. We examined the clearance of low-risk (lr) and high-risk (hr) cervical HPV infections, and the factors associated with these measures in HIV-negative and HIV-positive women. Methods We studied 630 Nigerian women involved in a study of HPV infection using short polymerase chain reaction fragment-10 assay and line probe assay-25. Research nurses used a cervical brush to collect samples of exfoliated cervical cells from all the study participants. Cox proportional hazards models were used to estimate associations between HIV and HPV infections. Results The mean age of the study participants was 38 (standard deviation, ± 8) years; 51% were HIV positive. The rate of clearing any HPV infection was 2.0% per month among all women in the study population, 2.5% per month among HIV-negative women, and 1.6% per month, among HIV-positive women. The clearance rate per 1,000 person-months of observation for any lrHPV infection and any hrHPV infection were 9.21 and 8.83, respectively, for HIV-negative women, and 9.38 and 9.37, respectively, for HIV-positive women. In multivariate models, the hazard ratios for HIV-positive compared with HIV-negative women were 0.85 (95% CI, 0.51 to 1.43; P = .55) and 0.95 (95% CI, 0.54 to 1.65; P = .85) for cleared infections with any lrHPV and any hrHPV, respectively. The hazard ratio for HIV-positive compared with HIV-negative women was 0.39 (95% CI, 0.17 to 0.88; P = .02) for cleared infections with any multiple HPV and 0.13 (95% CI, 0.03 to 0.58; P = .007) for cleared infections with multiple hrHPV. Conclusion In this study population, we observed that HIV-positive women were less likely to clear infections with multiple hrHPV types.

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14. Natural history of high-grade squamous intraepithelial lesions (HSIL) in homosexual men: early evidence from the Study of the Prevention of Anal Cancer (SPANC)

Sexual Health ◽

10.1071/shv10n6ab14 ◽

2013 ◽

Vol 10 (6) ◽

pp. 576 ◽

Cited By ~ 2

Author(s):

Andrew E. Grulich ◽

Fengyi Jin ◽

I. Mary Poynten ◽

Jennifer Roberts ◽

Annabelle Farnsworth ◽

...

Keyword(s):

Natural History ◽

Anal Cancer ◽

Cochrane Review ◽

Intraepithelial Neoplasia ◽

Hiv Positive ◽

Homosexual Men ◽

National Guidelines ◽

Anal Swab ◽

History Of ◽

Hiv Negative

Background Screening for the anal cancer precursor HSIL is not recommended in national guidelines. A recent Cochrane review of HSIL treatment concluded there is no evidence of efficacy. In this context, we aimed to describe the natural history of anal HSIL, and association with human papillomavirus (HPV), in a community-recruited cohort of Australian homosexual men. Methods: The SPANC study is a three-year prospective study in men aged ≥35 years. At each visit, men undergo an anal swab for cytology and HPV genotyping (Roche Linear Array), followed by high-resolution anoscopy-aided biopsy. Anal HSIL is defined as having either anal intraepithelial neoplasia grade 2/3 on histology and/or HSIL/ASC-H on cytology. Results: Among 342 men recruited by March 2013, median age was 49 with 29% HIV positive. At baseline, prevalence of anal HSIL was 50% and 44% in the HIV-positive and HIV-negative groups, respectively (P = 0.303). Among those without HSIL at baseline, HSIL incidence was 28/100 person-years in both the HIV-positive and HIV-negative groups (P = 0.920). Among those with HSIL at baseline, the incidence of change to non-HSIL was 41 and 43/100 person-years (P = 0.851). Men with anal HPV16 at baseline were more likely to develop incident HSIL (57 vs 23/100 person-years, P = 0.010), and less likely to change to non-HSIL (18 vs 61/100 person-years, P = 0.001). Conclusions: Anal HSIL was highly prevalent in these homosexual men. Both incidence of HSIL and change to non-HSIL were common, and were closely associated with HPV16 status. HPV16 positivity may identify men with HSIL at higher risk of anal cancer.

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